Passive drug infusion devices, in contrast to active ones, do not rely on a pump to deliver a drug but rather on a pressurized drug reservoir. A known problem of these passive devices is that the drug flow rate to a delivery location, which may be a patient's body for instance, may vary as a function of the amount of drug remaining in the reservoir as far as the pressure in the reservoir depends on this amount. Such passive devices are thus usually provided with a fluid flow regulator to ensure that the drug flow rate is as constant as possible with respect to the amount of drug remaining in the reservoir.
An example of such a passive drug flow regulator is available by the Applicant under the registered name “Chronoflow” and is disclosed in U.S. Pat. No. 6,203,523 B1. This device comprises a fluid inlet adapted to be connected to a fluid reservoir and a fluid outlet adapted to be connected to a patient's body. It comprises a rigid substrate and a resilient membrane tightly linked together in peripheral linking areas so as to define a cavity therebetween. This cavity is connected to the fluid outlet while the membrane has a first surface opposite the cavity which is connected to the fluid inlet. The membrane has a central through hole contiguous with the cavity, to define a pathway for a fluid from the fluid inlet to the fluid outlet, and is flexible so as to be able to come into contact with the substrate, in case a fluid would apply a pressure on the first surface that would be larger than a first predefined threshold value. As the membrane would come into contact with the substrate in the region of its central through hole, this would occlude the latter and result in hindering a fluid from flowing through it.
This device further comprises a flow regulator open channel etched in the substrate with an inlet facing the central through hole of the membrane and an outlet connected to the outlet of the device. This channel is in the shape of a spiral curve such that, the more pressure is applied against the membrane, the more it closes the channel thus forcing the fluid to flow in it to find its way out of the cavity. Consequently, when the pressure applied on the membrane increases, the length of the fluid pathway located within the flow regulator channel increases and so does the fluidic resistance of the device. Thus, the flow rate may be kept approximately constant within a predefined range in terms of the reservoir pressure.
However, fabrication of such a device is complicated and expensive. Indeed, the substrate has to be etched according to a specific pattern which is rather delicate regarding the accuracy level that has to be respected for the flow regulation to operate properly. Thus, not only the manufacture of the substrate requires specific extra-steps, but these steps are further delicate to carry out. Depending on the dimensions of the device, specific materials such as SOI is to be used for manufacture of the substrate, which is still more expensive.
Moreover, the device manufactured through this process is then designed for one specific set of parameters regarding delivery of a drug, i.e. predefined reservoir pressure range and average flow rate.
Hydrocephalus is usually due to blockage of CSF outflow in the ventricles or in the subarachnoid space over the brain. Hydrocephalus treatment is surgical: it involves the placement of a ventricular catheter (a tube made of silastic for example) into the cerebral ventricles to bypass the flow obstruction/malfunctioning arachnoidal granulations and the draining of the excess fluid into other body cavities, from where said fluid can be resorbed.
Most of the CSF shunts have been based on the principle of maintaining a constant intracranial pressure (ICP) regardless of the flow-rate of CSF. The CSF shunts have been constructed to cut off CSF-flow when the differential pressure between the inlet and the outlet of the CSF shunt was reduced to a predestined level, called the opening pressure of the shunt.
An example of an ICP shunt is shown in U.S. Pat. No. 3,288,142 to Hakim, which is a surgical drain valve device used to control the drainage of fluid between different portions of the body of a patient, particularly for draining cerebrospinal fluid from the cerebral ventricles into the blood stream (co called ventriculo-atriostomy).
Clinical experience has proven that this principle of shunting is not an ideal solution. Sudden rises of the ICP, e.g. due to change of position, physical exercise, or pathological pressure waves result in excessive CSF drainage. Several reports in the literature (Aschoff et al., 1995) point at problems due to this overdrainage, and especially the pronounced narrowing of the ventricles has been pointed out as being the main factor leading to malfunctioning of the implanted shunting device. The reason is that the ventricular walls may collapse around the ventricular CSF shunt device, and particles (cells, debris) may intrude into the shunt device.
U.S. Pat. No. 5,192,265 to Drake et al. describes an example of a shunt seeking to overcome the above-mentioned difficulties by proposing a rather complex anti-siphoning device allowing to select transcutaneously the resistance to flow by controlling the pressure in a chamber gas-filled and being in pressure communication with one flexible wall of the main chamber where the flow is regulated.
The use of programmable valves was associated with a reduction in the risk of proximal obstruction and overall shunt revision, one possible explanation for a difference in the two populations studied is that programmable valves may allow the physician to avoid such ventricular collapse by increasing the valve pressure setting after noting clinical signs and symptoms and/or radiological evidence of overdrainage. In this way, proximal obstruction is prevented, and shunt revision surgery is avoided. One such adjustable valve is described in U.S. Pat. No. 4,551,128 to Hakim et al. However, due to the elastomeric properties of the diaphragm material, maintenance of the implanted valve may be required. Further, flow rate adjustment of this adjustable valve after implantation may require a surgical procedure.
Another adjustable valve mechanism, described in U.S. Pat. No. 4,781,673 to Watanabe, includes two parallel fluid flow passages, with each passage including a flow rate regulator and an on-off valve. Fluid flow through the passages is manually controlled by palpably actuating the on-off valves through the scalp. Although the Watanabe device permits flow rate control palpably through the scalp and thus, without surgical intervention, patient and/or physician attention to the valve settings is required.
One system, described in U.S. Pat. No. 6,126,628 to Nissels, describes a dual pathway anti-siphon and flow-control device in which both pathways function in concert. During normal flow, both the primary and secondary pathways are open. When excessive flow is detected, the primary pathway closes and flow is diverted to the high resistance secondary pathway. The secondary pathway decreases the flow rate by 90% while maintaining a drainage rate within physiological ranges, which prevents the damaging complications due to overdrainage. However, this device is intended for use with a shunt system including a valve for controlling flow rate and should be placed distal to the valve inducing cumbersome procedure due to the additional material to be implanted. The system can be used as a standalone only for low-pressure flow-control valve.